LAUSR

Background: Over-expression of membranous CD154 and soluble CD154 (sCD154) in T lymphocytes is important in pathogenesis of autoimmune diseases. PKC pathway induces sCD154 production through promoting shedding of membranous CD154. Objectives: Hydroxychloroquine (HCQ) has been used in the treatment of autoimmune diseases for decades. We sought to identify the effects of HCQ on sCD154 and a possibly regulatory mechanism. Methods: CD4 +T cells were isolated from the blood of healthy donor. After stimulated with ionomycin +PMA and various concentrations of HCQ, concentration of sCD154 in the medium, expression of membranous CD154, Ca2+ pathway and PKC signalling pathway were assessed. Results: HCQ attenuated intracellular sustained calcium storage release and membranous CD154 synthesis in activated T cells. Besides, HCQ inhibited PKC activation and subsequently shedding of membranous CD154. Conclusions: HCQ inhibited production of sCD154 in activated T cells through suppressing Ca2+ and PKC signalling pathway. These findings provide one of the mechanistic insights into HCQ treatment. References [1] Alaaeddine N, Hassan GS, Yacoub D, Mourad W. CD154: an immunoinflammatory mediator in systemic lupus erythematosus and rheumatoid arthritis. Clin Dev Immunol. 2012:490148. [2] Goules A, Tzioufas AG, Manousakis MN, Kirou KA, Crow MK, Routsias JG. Elevated levels of soluble CD40 ligand (sCD40L) in serum of patients with systemic autoimmune diseases. J Autoimmun2006;26:165–71. [3] Matthies KM, Newman JL, Hodzic A, Wingett DG. Differential regulation of soluble and membrane CD40L proteins in T cells. Cell Immunol. 2006;241:47–58. [4] Wu SF, Chang CB, Hsu JM, Lu MC, Lai NS, Li C, Tung CH. Hydroxychloroquine inhibits CD154 expression in CD4+ T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther2017Aug 9;19(1):183. Disclosure of Interest None declared